The present invention relates to the identification of freeze-dried dosage forms. More particularly, the present invention relates to the embossment of porous freeze-dried dosage forms by embossing the base of a blister pocket and forming a freeze-dried unit in the embossed blister pocket, whereby the embossment on the blister pocket is transferred to the dosage form during the freeze-drying process.
Medication in forms such as tablets, capsules, caplets or freeze-dried dosage forms has been typically packaged in blister packages or sheets of multiple blister pockets or compartments. A base sheet of transparent or opaque plastic, for instance polyvinyl chloride (PVC or PVC type laminates), will frequently have a plurality of blister pockets projecting from one face thereof, for containing the unit dosages of medication.
If the units of medication to be packaged in the blister package are solid units such as tablets, capsules or caplets, the solid units may simply be deposited into the blister pockets of the base sheet. On the other hand, if the units to be packaged are freeze-dried dosage forms, then the medication may be closed and frozen directly within the blister pockets and then dried therein using a freeze-drying process, as explained by Gregory et al., U.S. Pat. No. 4,305,502. The freeze-drying process is well known in the art and may involve first dosing a liquid suspension into the pre-formed blister pockets of the base sheet. The base sheet containing the suspension is then cooled by a medium such as liquid nitrogen or carbon dioxide, thereby freezing the contents of the blister pockets. The frozen contents may then be subjected to reduced pressure to complete the freeze drying process.
The pharmaceutical industry abounds with a variety of dosage forms, many of which are very similar, if not identical, to each other in outward appearance. It is therefore often necessary to place an identifying logo, code or other mark on each individual dosage form. Such mark might identify the manufacturer, the brand name, the active component strength or any other useful information regarding the dosage form. Further, several states in the United States of America currently require certain identifying markings to appear on individual units of medication.
Solid units of medication such as tablets, capsules or caplets have been acceptably identified by printing information directly onto the unit. Alternatively, solid units have been embossed with an identifying mark by compressing an embossment into the surface of the unit. The latter method is illustrated by or analogous to the processes disclosed by U.S. Pat. Nos. 3,534,440 (Roberts), 2,645,852 (Weinberg) and 510,453 (Tobin).
The Roberts patent "relates to the manufacture of bodies of materials formable by pressing, more particularly but not exclusively soap and synthetic detergent bars, tablets and the like." (Col. 1, lines 29-32). In particular, the Roberts patent teaches a process that incorporates an apparatus comprised of (1) a lower die having a cavity, the planar bottom surface of the cavity serving as a lower "pressing face," and (2) an upper die whose planar underside serves as an upper "pressing face." A strip of thin embossed material is affixed to either the lower pressing face or the upper pressing face (or both). The body of material to be formed and embossed is then placed into the cavity, and the upper and lower dies are "brought together under positive pressure until [the] die surfaces . . . abut. [The body] is thereby shaped to final form and at the same time its upper [and/or lower] surface engaged by [the embossed strip] is formed with indented indicia corresponding to the projecting characters . . . on the embossed strip." (Col. 3, lines 59-65).
The Weinberg patent teaches a device for the manufacture of "pats or chips from a block of butter, oleomargarine, or the like soft, plastic, easily incisible material." The device generally comprises a base having upwardly extending walls or flanges, a cover telescopically but loosely fitting over the base, and an "impressor" plate removably mounted within the cover. The base and cover are made of metal or, preferably, plastic capable of being warmed sufficiently to prevent the cover and base from sticking to the butter. The impressor plate may be "formed with ribs for dividing the slab [of butter] into a plurality of separate pats or chips for impressing a design into the several pats." (Col. 1, lines 14-17). Butter is placed in the base, and the cover is positioned and pressured down, thereby causing the impressor plate to emboss a given design onto the butter.
Tobin discloses a butter molding machine, "the purpose of [which] is to provide improved mechanism for rapidly molding butter, or similar substance, into small disks or `pats.`" (Col 1, lines 10-13). In general, the invention is comprised of (1) an upright cylinder that is charged with butter, the cylinder having a mouth at its top for emitting the butter, and a piston disposed in the cylinder for forcing the butter out of the mouth; and (2) a plate having one or more mold cavities to be filled with butter emitted from the mouth of the cylinder and to impart a shape and pattern to the resulting butter pats. Upward pressure is applied to the piston to force the butter out of the mouth of the cylinder and into the mold cavities. "[T]he pressure upon the piston is made sufficient to produce the complete imprint of the dies upon each pat of butter thus molded." (Col 5, lines 10-13).
While the above-illustrated printing and direct compression methods are well suited to the application of an identifying mark to most solid units of medication, such methods are ill-suited to applying an identifying mark to porous freeze-dried units. In particular, it has been determined that, due to the inherent fragility, surface undulation, moisture sensitivity and chemical makeup of freeze-dried dosage forms, the application of compression would cause deformation, reduced porosity and hence increased dispersion time, and possibly cracking of the dosage forms. Similarly, it is believed that the chemical makeup, moisture sensitivity, porosity and surface undulation of freeze dried dosage forms would cause ink to dissolve the dosage forms at the point of contact or to diffuse throughout the dosage forms leading to clarity problems. A need therefore exists for a method of applying an identifying mark to the surface of freeze-dried pharmaceutical units.
Accordingly, it is a primary objective of the present invention to provide a method of identifying freeze-dried dosage forms.
It is another objective of the present invention to provide a method of applying an identifying mark to a freeze-dried unit during the freeze-drying process.
It is yet another objective of the present invention to provide a method of preparing an embossed freeze-dried dosage form without cracking or otherwise deforming or dissolving the dosage form.
It is a further objective of the present invention to provide a method of embossing a freeze-dried unit of medication during the process of freeze-drying the unit in a blister pocket.
It is still a further objective of the present invention to provide a reduced cost method of manufacturing a combination of an embossed blister pocket and an embossed freeze-dried unit contained in the blister pocket.
Further objects and advantages of the present invention will become apparent in the following description.